ABSTRACT Approximately 15% of North American couples experience infertility, defined clinically as the inability to conceive after 12 months of unprotected intercourse. Fertility treatments have modest success rates, create a large psychological and financial burden for those affected, and cost over $5 billion annually in the United States. Male factor contributes to 50% of infertility, but there has been little epidemiologic research on predictors of male infertility. In addition, male participation in epidemiologic research has been low. We propose to harmonize and analyze data from two interrelated NICHD-funded prospective cohort studies of time-to-pregnancy (TTP) among couples in Denmark (Snart Foraeldre) and North America (Pregnancy Study Online, PRESTO). In these cohorts, we have already recruited 1,200 male participants aged ?21 years and their female partners. With these data, we propose to evaluate prospectively the relation of selected exposures to male fecundability, focusing on lifestyle and psychosocial factors that are novel or understudied, or for which existing studies are inconclusive. Specific exposures of interest include cell phone use, active and passive smoking, alcohol consumption, perceived stress, occupational stress, sleep quality and duration, depression, and anxiety. Comprehensive data have been collected on men and their female partners, with regular follow-up among females every two months for up to 12 months or until pregnancy is reported. Follow-up questionnaires allow for the prospective ascertainment of TTP and the updating of covariates. While there have been many studies investigating the effects of male lifestyle on infertility, virtually all of these studies have been conducted in men seeking fertility treatment, men living in urban centers, and white non-Hispanic men, thereby limiting generalizability. Moreover, the few existing prospective studies of male TTP are small and underpowered. The present study will address these limitations. The enrollment of large numbers of men from the general population, representing the full fertility spectrum and residing in all geographic regions of the United States, Canada, and Denmark, creates a unique opportunity to assess male risk factors for infertility in our cohorts. In addition, our study enrolls couples before conception, thereby reducing biases due to exposure misclassification, left truncation, and differential recall. The harmonization of large preconception cohorts with similar designs will provide excellent power to evaluate a broad range of hypotheses. This will be the largest prospective preconception cohort study of modifiable risk factors for male infertility to date. Findings from the proposed research are likely to have a large and sustained impact on the field and will result in actionable recommendations for couples to improve their fertility.